Arid1a-dependent canonical BAF complex suppresses inflammatory programs to drive efficient germinal center B cell responses.

Autor: Abraham A; Department of Cell and Developmental Biology, Northwestern University, Chicago, IL, USA.; Center for Human Immunobiology, Northwestern University, Chicago, IL, USA., Samaniego-Castruita D; Department of Cell and Developmental Biology, Northwestern University, Chicago, IL, USA., Han I; Department of Cell and Developmental Biology, Northwestern University, Chicago, IL, USA., Ramesh P; Department of Cell and Developmental Biology, Northwestern University, Chicago, IL, USA., Tran MT; Department of Cell and Developmental Biology, Northwestern University, Chicago, IL, USA., Paladino J; Department of Cell and Developmental Biology, Northwestern University, Chicago, IL, USA., Kligfeld H; Department of Cell and Developmental Biology, Northwestern University, Chicago, IL, USA., Morgan RC; Department of Cell and Developmental Biology, Northwestern University, Chicago, IL, USA., Schmitz RL; Department of Cell and Developmental Biology, Northwestern University, Chicago, IL, USA., Southern RM; Department of Cell and Developmental Biology, Northwestern University, Chicago, IL, USA., Shukla A; Department of Cell and Developmental Biology, Northwestern University, Chicago, IL, USA., Shukla V; Department of Cell and Developmental Biology, Northwestern University, Chicago, IL, USA. vipul.shukla@northwestern.edu.; Center for Human Immunobiology, Northwestern University, Chicago, IL, USA. vipul.shukla@northwestern.edu.; Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA. vipul.shukla@northwestern.edu.
Jazyk: angličtina
Zdroj: Nature immunology [Nat Immunol] 2024 Sep; Vol. 25 (9), pp. 1704-1717. Date of Electronic Publication: 2024 Aug 14.
DOI: 10.1038/s41590-024-01920-y
Abstrakt: The mammalian Brg1/Brm-associated factor (BAF) complexes are major regulators of nucleosomal remodeling that are commonly mutated in several cancers, including germinal center (GC)-derived B cell lymphomas. However, the specific roles of different BAF complexes in GC B cell biology are not well understood. Here we show that the AT-rich interaction domain 1a (Arid1a) containing canonical BAF (cBAF) complex is required for maintenance of GCs and high-affinity antibody responses. While Arid1a-deficient B cells undergo initial activation, they fail to sustain the GC program. Arid1a establishes permissive chromatin landscapes for B cell activation and is concomitantly required to suppress inflammatory gene programs. The inflammatory signatures instigated by Arid1a deficiency promoted the recruitment of neutrophils and inflammatory monocytes. Dampening of inflammatory cues through interleukin-1β blockade or glucocorticoid receptor agonist partially rescued Arid1a-deficient GCs, highlighting a critical role for inflammation in impeding GCs. Our work reveals essential functions of Arid1a-dependent cBAF in promoting efficient GC responses.
(© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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